Leukaemia Foundation Research Unit
The goal is simple. Find cures for blood cancers and related disorders and deliver the benefits to people quickly.
Established in 1992, the Unit is located at the Queensland Institute of Medical Research (QIMR) on the Royal Brisbane Hospital campus. This enables the laboratory to draw on other world-class research at the insitute, one of the largest in the southern hemisphere, and on first-rate facilities at surrounding hospitals.
To date, the Leukaemia Foundation has invested $3.8 million in the laboratory, contributing $350,000 each year or around one third of annual running costs.
The laboratory is led by Professor Andrew Boyd, Professor of Experimental Haematology who is recognised internationally as a leader in haematological cancer research. Professor Boyd’s vision is that the lab will become a centre of excellence in molecular biology and the hub of expanding haematological research centre.
The laboratory seeks to:
- explore the basic causes of these diseases
- use this knowledge to develop novel theories; and
- improve the expertise needed to rapidly evaluate and implement new ideas
Currently, the laboratory is exploring the biology of leukaemia and other cancers through studies of leukaemia-associated proteins. These are proteins which are either modified forms of normal proteins or are proteins which are normally not seen on blood cells but are abnormally expressed by leukaemic cells. In some cases these proteins are also expressed on other cancers.
Under the direction of Professor Andrew Boyd and previously, Australia’s first Professor of Experimental Haematology, Professor Johnson, the research team has grown from four to 25.
“It is the continuous financial input from the Leukaemia Foundation that allows the lab to do the crucial development work – the really new stuff that might take five years to get off the ground but which could lead to something new – like a new drug. A new age is dawning in the treatment of leukaemia.” Professor Andrew Boyd
The laboratory discovered EphA3 in the cancer cells of a person with childhood leukaemia. This gene is not normally active in blood cells but is highly expressed in a number of leukaemias and lymphomas. It has now shown that a proportion of other cancers also express EphA3, but that it is not expressed in any normal tissues at significant levels. The team is investigating this gene and a number of other members of the large Eph gene family.
- EphA3 in cancer therapy – the team is investigating a monoclonal antibody directed at EphA3 as a potential anti-cancer therapy. In a pre-clinical leukaemia model this has proved very effective at inhibiting leukaemia cell growth, and the team is now working with a US company on a form of the antibody which could be used in humans.
- EphA1 and 2 in tissue function & cancer – two other members of the family found in blood cells are also being investigated. Both are also found to be abnormally expressed in some cancers. The team has developed antibodies to each of these to explore the distribution in leukaemia and other cancers.
- EphA4 – the laboratory has made an extensive study of EphA4 which is expressed in blood cells, particularly the cells which give rise to platelets. It has shown that this is also very important in normal spinal cord development. The team is working with other scientists at University of Queensland on potential treatments for spinal injuries while continuing to to look at EphA4 expression in leukaemias and in normal blood cells.
Bcl-2 family proteins in tumours
Most normal cells are programmed to die at a certain age or stage of development through a biochemical process called apoptosis. Up to that point the cells are protected by anti-apoptosis proteins including Bcl-2 and related proteins, one of which is Mcl-1. Some cancers over-express one or more of these proteins as a way of preventing apoptosis, thus allowing the tumour to survive and grow inappropriately. In leukaemias, including chronic lymphocytic leukaemia (CLL), high levels of Mcl-1 appear to correlate with a more aggressive course.
- Inhibiting Mcl1 in tumours – the team is studying the effect of inhibiting Mcl-1 on tumour survival. These studies show that “knocking down” Mcl-1 can sensitise tumour cells to chemotherapy and other agents which trigger the apoptosis mechanism.
- Mcl1 promoter analysis – these studies have shown that the mechanism of switching on the Mcl-1 gene is more complex than previously recognised. Indeed, these studies show that the proposed mechanism thought to explain over-expression in CLL is incorrect. The team has identified a transcription factor binding site in the gene which has a major effect on Mcl-1 expression.
Fat protocadherin in T ALL/lymphoblastic lymphoma
These forms of acute leukaemia are still devastating in most people and there is an urgent need for new therapeutic approaches. The Unit has shown that most cases express an abnormal form of the Fat protocadherin protein. This abnormal form has a unique structure and investigations continue as to whether this is a therapeutic target.
The Unit also contributes to a number of pre-clinical studies and early phase clinical trials of agents developed by other groups (academic and commercial). These studies are important in developing new therapies here in Australia and are also critical in bringing in the expertise to translate research along the clinical development pathway.